Epidemiology

• Incidence is 3-4 per million subjects per year.^[1]
• Acromegaly most often occurs in adults aged 40-45 years.^[2]

Presentation

Often an insidious onset and symptoms may precede the diagnosis by several years.

• Due to tumour:
  • Headaches.
  • Visual field defects: the most common defect is a bitemporal hemianopia.
• Due to excess of growth hormone:
  • Gradual change in appearance due to the effects on cartilage and soft tissues: enlargement of hands and feet (increase in ring and shoe size), frontal bossing, thickening of the nose, enlarged tongue (macroglossia), growth of the jaw (prognathism), and coarsening of facial features.
  • Macroglossia may cause obstructive sleep apnoea leading to daytime tiredness.
  • Excessive sweating and oily skin, with development of skin tags. Women may have mild hirsutism.
  • Articular overgrowth of synovial tissue and arthropathy leading to arthritis (widespread osteoarthritis of the weight-bearing joints), back pain and kyphosis.
  • Visceral hypertrophy, eg heart, liver, thyroid (with a multinodular goitre), prostate and kidneys.
  • Nerve compression symptoms may occur, especially carpal tunnel syndrome.
  • Cardiac features include hypertension, left ventricular hypertrophy, cardiomyopathy and arrhythmias.
• Due to associated hyperprolactinaemia, eg galactorrhoea, amenorrhoea.
• Hypopituitarism: decreased secretion of anterior pituitary hormones and compression of pituitary stalk.

Investigations

See also separate article Pituitary Function Tests.

• Visual field tests.
• Blood glucose; serum phosphate, urinary calcium and serum triglycerides may also be raised.
• Assessment of growth hormone:
  • Random growth hormone: often not diagnostic because of episodic secretion and short half-life of the hormone.
  • Glucose tolerance test: growth hormone (GH) is normally inhibited by glucose. If the glucose load fails to suppress the GH level below 0.3 mcg/L and the insulin-like growth factor-I (IGF-I) level is elevated, then the diagnosis of acromegaly can be confirmed.^[3]
  • IGF-I: long half-life and so is a useful measurement to assess growth hormone secretion and therefore screen for acromegaly and monitor the effect of therapy.^[4]
  • IGF-binding protein-3 (IGFBP-3): is the main binding protein for circulating IGF and is increased in acromegaly. Can be useful in the diagnosis of acromegaly.
  • Growth hormone-releasing hormone (GHRH) concentration can be obtained if clinically indicated.
• Assessment of other pituitary hormones: prolactin, adrenal, thyroid, and gonadal hormones.
• MRI scan of pituitary and hypothalamus: more sensitive than CT scan.
• CT scan: for lung, pancreatic, adrenal or ovarian tumours that may secrete ectopic growth hormone or GHRH.
• Total body scintigraphy with radio-labelled OctreoScan® (somatostatin) to aid localisation of the tumour.
• Cardiac assessment: electrocardiogram, echocardiogram.

Differential diagnosis

Pseudo-acromegaly is the presence of a similar physical appearance in the absence of elevated growth hormone or insulin-like growth factor-I (IGF-I). Causes of pseudo-acromegaly include insulin resistance associated with hyperinsulinaemia and minoxidil treatment.^[6][7]

Management

The aim of management is to control the symptoms caused by the local effects of the tumour and due to the excess hormone production, and to normalise hormone levels. No single treatment is completely effective in achieving these aims and so a combination of treatments is required, usually with surgery as first-line treatment and drug treatment for residual disease.^[2]

• Trans-sphenoidal surgery is the treatment of choice in most cases. Remission rates are 80-85% for microadenomas and 50-65% for macroadenomas.^[8] Patients with residual disease can then be offered adjuvant treatment.
• Patients may need drug treatment after surgery in order to reduce growth hormone levels.
• Radiotherapy is used for refractory disease, as an adjuvant for large invasive tumours and when surgery is contra-indicated.

Drug treatment^[9]

• Somatostatin analogues:
  • Octreotide and lanreotide are analogues of the hypothalamic release-inhibiting hormone somatostatin.
  • Growth hormone-secreting pituitary tumours can expand during treatment and patients should therefore be monitored for signs of tumour expansion, eg regular assessment of visual fields.
• Dopamine agonists: bromocriptine and cabergoline are effective but are less effective than somatostatin analogues.^[10] Tumours that also secrete prolactin have a better response rate to dopamine agonists.
• Pegvisomant:
  • Genetically modified analogue of human growth hormone and is a highly selective growth hormone receptor antagonist.
  • Has been shown to normalise insulin-like growth factor-I (IGF-I) levels in 90-100% of patients.
  • Growth hormone levels increase during treatment and no decrease in tumour size is seen.
  • Pegvisomant is licensed for the treatment of acromegaly in patients with inadequate response to surgery, radiotherapy or somatostatin analogues.

Complications

• Ischaemic heart disease, cardiac failure, cerebrovascular disease.
• Diabetes.
• Acromegalic arthropathy, which affects up to 70% of patients and involves both the axial and peripheral skeleton.^[1]
• Obstructive sleep apnoea.
• Increased incidence of colonic polyps and adenocarcinoma of the colon.^[1]
• Patients may develop hypopituitarism immediately after surgery, or several years after radiotherapy.
• Damage caused by the tumour may result in hyperprolactinaemia and deficiencies of glucocorticoids, sex steroids and thyroid hormone.
• Pregnancy in women with active or uncontrolled acromegaly may be associated with an increased risk of gestational diabetes and gravid hypertension.^[11]

Prognosis

• High levels of growth hormone, even when the patient has no symptoms, are associated with a 2- to 3-fold increase in mortality.^[12]
• Tumour size: microadenoma (tumour less than 10 mm) is associated with a better prognosis than macroadenoma, mainly because persistence of disease after surgery is more common with macroadenomas.
• Remission rates for microadenomas are in the region of 80-85% and 50-65% for macroadenomas, depending on the initial size of the tumour, the growth hormone level, and the skill of the neurosurgeon. Higher postoperative growth hormone concentrations are associated with a worse prognosis.^[2]
• Hypertension, cardiovascular disease, diabetes and long duration of symptoms are also poor prognostic factors.